Young subjects consuming high-THC cannabis strains (e.g., sinsemilla) were more likely to develop anxiety and cannabis use disorder as well as to experience psychiatric-like symptoms and frequent relapses. Over the past decades, THC concentration has increased progressively while no changes were observed in the levels of cannabidiol (CBD), the main non-psychoactive constituent of cannabis and which has been found to protect against various THC-related effects. Importantly, the relative potency of THC appears to have a crucial role in cannabis pathology. Specifically, developmental THC exposure has been associated with a wide range of cognitive impairments and enhanced vulnerability for neuropsychiatric disorders, concomitant with significant neuroanatomical abnormalities and maladaptations in the mesocorticolimbic system. Ĭlinical and pre-clinical evidence has revealed numerous long-lasting detrimental effects induced by chronic cannabis use during adolescence. Notably, while CB1R endogenous ligands, such as anandamide (AEA), are subjected to metabolic control through a complex system of biosynthetic and degradative enzymes, THC largely escapes these neuroregulatory control mechanisms, resulting in more sustained and less regulated neurophysiological effects. In fact, sustained exposure to the main psychoactive marijuana phytochemical, Δ-9-tetrahydrocannabinol (THC), induces overstimulation of cannabinoid receptors type 1 (CB1Rs) and may profoundly impact the physiological development of the endocannabinoid system (ECS). These trends are highly concerning given that age of onset, frequency, and duration of exposure have been reported as significant risk factors for a wide array of cannabis-related pathophenotypes.

75% in 2019) believed that daily cannabis smoke can increase the vulnerability for mental health disorders. Such findings were concomitant with a reduction in perceived risks, since fewer participants (66% in 2020 vs. In addition, a recent Canadian Cannabis Survey reported that, in 2020, the percentage of cannabis use in youth (16 to 24 years) was approximately two-fold higher than in older people (>25 years), and 31% of people aged 16 to 19 and 20 to 24 reported increased consumption of cannabis due to COVID-19. Analysis of cannabis use revealed that in European countries up to one-third of adolescents (12 to 17 years) smoke cannabis and 1.2% of them consume it regularly, whereas a progressive increase of use from 14% to 44% was reported among high school American teens. Adolescence is a period of profound neurodevelopmental vulnerability in which crucial structural and functional neural changes occur, but it is also a common life-stage for drug experimentation. The increasing legalization of marijuana around the world strengthens the need to pursue clinical and pre-clinical investigations into its potential detrimental consequences, especially in developing brains. This narrative review will summarize recent clinical and pre-clinical evidence that has elucidated these THC-induced developmental risk factors and examine how specific pharmacotherapeutic interventions may serve to reverse or perhaps prevent these cannabis-related risk outcomes.Ĭannabis is one of the most widely used psychoactive drugs for recreational and medical purposes.

A common theme among these studies is the ability of developmental THC exposure to induce long-term adaptations in the mesocorticolimbic system which resemble pathological endophenotypes associated with these disorders. Clinical and pre-clinical research continues to identify a wide array of underlying neuropathophysiological sequelae and mechanisms that may underlie THC-related psychiatric risk vulnerability, particularly following adolescent cannabis exposure.

This increased risk includes a higher prevalence of schizophrenia, mood and anxiety disorders, and cognitive impairments. Neurodevelopmental exposure to psychoactive compounds in cannabis, specifically THC, is associated with a variety of long-term psychopathological outcomes.

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